The goal of the proposed research is to solve the problem of developing computationally efficient image reconstruction algorithms for noncontact optical tomography (OT) with large data sets. Specifically, we intend to devise fast algorithms for three-dimensional image reconstruction at the megavoxel level. To achieve this goal, we will exploit recent advances obtained by the Investigators on analytic methods for image reconstruction in OT. The algorithms will be systematically studied by computer simulations and validated by experiments in model systems. This approach allows the separation of effects due to algorithmic errors from those due to measurement errors. The planned "benchtop" experiments are the next logical step after algorithm development but before clinical studies and are critical to the success of this proposal. The specific aims are to (1) Construct instrumentation for multispectral noncontact optical tomography. This will entail upgrading an existing single-wavelength continuous-wave OT system. The planned enhancements include an electron multiplying CCD camera for faster data acquisition and improved signal to noise;illumination at three wavelengths using optically switched diode lasers;and time-resolved transmission measurements using a pulsed Ti-sapphire laser for spectroscopic measurements of absorption and scattering;(2) Implement and optimize fast image reconstruction algorithms for OT with large data sets. The planned studies will first focus on nonlinear reconstruction of the absorption. The focus will then shift to simultaneous linear and nonlinear reconstruction of absorption and scattering using multispectral and multifrequency data. The algorithms will be tested and optimized using numerical simulations prior to experimental validation in phantoms;(3) Evaluate the performance of the above reconstruction algorithms using phantoms. The reconstruction algorithms will be tested in a set of experiments which parallel the numerical simulations carried out under specific aim 2. Image quality will be assessed in tissue-equivalent phantoms. We will utilize the parallel plate imaging geometry which is often employed in optical mammography. The results of this research are expected to impact the design of clinically useful instruments for noncontact optical tomography.